Heat-Shock-Induced Changes in Nuclear Protein and Cell Killing in Thermotolerant HeLa Cells

The correlation between the protein content of nuclei and heat-induced cell killing was determined for HeLa cells with various levels of thermotolerance. Thermotolerance was induced by heating cells at 45°C for 15 or 30 min and then incubating them at 37°C for 5 or 24 h. This procedure resulted in four different levels of thermotolerance requiring up to 5 h of heat at 45°C to kill more than 90% of the most resistant cells. Upon exposure to 45°C, the increase in the protein content of isolated nuclei was proportionally less for thermotolerant cells. The difference between the initial increase in nuclear protein content for normal and thermotolerant cells was relatively small for shorter heating times but became clearly evident for longer heating exposures. The correlations between cell killing and nuclear protein content were not statistically different from controls for any of the various levels of thermotolerance. The correlation was measured over survival levels below 0.1 in thermotolerant cells. Because thermotolerant HeLa cells are very resistant to heat, previous studies had not tested the correlation to survival levels below a half-decade of cell killing. These results should resolve some of the conflicting observations reported in the literature and are consistent with the suggestion that heat-induced changes in binding of nuclear protein play a key role in the lethal effects of hyperthermia.